The Free State is hardest hit by medicine shortages for HIV and tuberculosis, the Treatment Action Campaign said on Thursday.
"The premier must put and end to the chronic shortage of medicines in the Free State health system," TAC national chair Anele Yawa said in Bloemfontein.
Several members of the TAC marched to Free State premier Ace Magashule's office in the city to hand over a memorandum urging him to intervene in Free State health matters.
The group also urged Magashule to urgently address the staff shortages in the provincial health system.
Yawa said Magashule should dismiss health MEC Benny Malakoane because he had an "unco-operative attitude towards civil society".
The TAC also wanted Magashule to condemn all threats of violence and attempts to intimidate TAC members speaking out on the province's health system.
A director in Magashule's office received the memorandum on his behalf.